MicroRNA-339-5p inhibits colorectal tumorigenesis through regulation of the MDM2/p53 signaling

Cen Zhang, Juan Liu, Xiaolong Wang, Rui Wu, Meihua Lin, Saurabh V. Laddha, Qifeng Yang, Chang S. Chan, Zhaohui Feng

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Tumor suppressor p53 plays a central role in tumor suppression. To ensure its proper function, the levels and activity of p53 are under a tight regulation in cells. MicroRNAs are short non-coding RNAs that play an important role in regulation of gene expression. Recently, microRNA-339-5p has been reported to be frequently down-regulated in colorectal cancer, and furthermore, its down-regulation is associated with poor prognosis in cancer patients, which strongly suggests a tumor suppressive function of microRNA-339-5p in colorectal cancer. In this study, we found that microRNA-339-5p directly represses the expression of MDM2, a key negative regulator of p53, through binding to MDM2 3'-UTR in colorectal cancer cells. Through the down-regulation of MDM2, microRNA-339-5p increases p53 protein levels and functions, including p53 transcriptional activity and p53-mediated apoptosis and senescence in response to stress. Furthermore, microRNA-339-5p inhibits the migration and invasion of colorectal cancer cells and the growth of colorectal xenograft tumors in a largely p53-dependent manner. Our results highlighted an important role of microRNA-339-5p in suppression of colorectal tumorigenesis, and also revealed that regulating the p53 function is an important mechanism for microRNA-339-5p in tumor suppression.

Original languageEnglish (US)
Pages (from-to)9106-9117
Number of pages12
JournalOncotarget
Volume5
Issue number19
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

  • Colorectal cancer
  • Invasion
  • Migration
  • P53
  • Tumorigenesis
  • microRNA-339-5p

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